3-Methyl-l-phenyl-2-pyrazolin-5-one (non-proprietary name: “Edaravone”, trade name: “Radicut”; manufactured and sold by Mitsubishi Pharma Corporation. hereinafter referred to as Edaravone) which is one of the pyrazolone derivatives as mentioned above is also called 3-methyl-1-phenyl-5-pyrazolone. It is a compound recognized to have potent effectiveness in the various experiments using animal models of cerebrovascular disorders and its clinical application is extremely expected as a drug for the treatment of cerebrovascular disorders such as cerebral stroke, brain tumor, cerebral ischemia observed in the acute stage of head trauma, cerebral edema and the like for which no effective drug is available {brain function normalizing effect (Japanese patent publication (Kokoku) No. Hei 5-31523), lipid peroxidation inhibiting effect (Japanese patent publication (Kokoku) No. Hei 5-35128). An injection containing Edaravone as an active ingredient has been developed. One example is an injection which is an aqueous solution of Edaravone containing at least one compound selected from sulfites, hydrogensulfites and pyrosulfites, and a cysteine and has a pH in the range of 2.5 to 6.0 (Japanese patent publication (Kokoku) No. Hei 7-121861).
Now, Edaravone is clinically used as a brain protector (infusion) and two ampoules are needed daily. If Edaravone is prescribed for the other diseases in future, there are possibilities of using more ampoules. Anyway, in the present prescription, it is necessary to prepare at least two ampoules or vials a day. However, in the medical treatment site where any medical accidents must be avoided, the number of steps required for the preparation of medicines should be reduced as much as possible and the availability of the medicines should be increased. Further, medicines each composed of plural ampoules or vials need a wider space to store them in. Such a situation is not preferable for both a medicine maker and one engaged in the medical treatment.
There is accordingly a demand for the development of a medicine containing high-concentration of Edaravone but low in volume, namely, a high concentration low volume injection. However, Edaravone is sparingly soluble in water (2 mg/mL at 25° C.), has less chemical stability with an increase in its concentration in the aqueous solution, and is apt to be decomposed by oxidation in the aqueous solution compared to Edaravone in the powder form. In consideration of such properties, it is difficult to stabilize Edaravone as a pharmaceutical for a long period time and prepare an injection containing it in an amount exceeding a saturated solubility in water. Actually, such a formulation is not realized until now.